11-71538141-G-A

Position:

• chr11-71538141-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021046.3(KRTAP5-8):​c.86G>A​(p.Cys29Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: KRTAP5-8 NM_021046.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.39

Genes affected

KRTAP5-8 (HGNC:23603): (keratin associated protein 5-8) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19052508).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP5-8	NM_021046.3	c.86G>A	p.Cys29Tyr	missense_variant	1/1	ENST00000398534.4	NP_066384.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP5-8	ENST00000398534.4	c.86G>A	p.Cys29Tyr	missense_variant	1/1		NM_021046.3	ENSP00000420723	P1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 144

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 06, 2024

The c.86G>A (p.C29Y) alteration is located in exon 1 (coding exon 1) of the KRTAP5-8 gene. This alteration results from a G to A substitution at nucleotide position 86, causing the cysteine (C) at amino acid position 29 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	5.8
DANN	Benign	0.84
DEOGEN2	Benign	0.087	T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.019
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.0	M
MutationTaster	Benign	0.97	N
PROVEAN	Pathogenic	-7.9	D
REVEL	Benign	0.12
Sift	Benign	0.17	T
Sift4G	Uncertain	0.0080	D
Polyphen		0.89	P
Vest4		0.11
MutPred		0.46		Gain of glycosylation at S26 (P = 0.1579);
MVP		0.32
MPC		0.066
ClinPred		0.92	D
GERP RS		1.6
Varity_R		0.23
gMVP		0.037

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-71249187;